Neuraminidase inhibitors for treatment of human and avian strain influenza: A comparative modeling study
Neuraminidase inhibitors for treatment of human and avian strain influenza: A comparative modeling study
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DOI：
10.1016/j.jtbi.2010.10.017
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发表时间：
2011-01-21
影响因子：
2
通讯作者：
Beauchemin, Catherine A. A.
中科院分区：
文献类型：
--
作者：
Dobrovolny, Hana M.;Gieschke, Ronald;Beauchemin, Catherine A. A.
使用抗病毒药物如神经氨酸酶抑制剂（NAI）治疗季节性流感病毒感染已被证明是有效的，如果在感染后48小时内给药。然而，越来越多的证据表明，即使在感染后6天（dpi），对禽源性毒株感染进行抗病毒治疗也可以显着降低感染的严重程度和持续时间。使用一个数学模型，在宿主流感病毒感染，可以捕捉到一个短暂的，典型的，季节性感染和严重的感染表现出持续的病毒滴度的动力学，我们探讨了NAI治疗对两种类型的流感病毒感染的影响的差异。将我们的模型的行为与自然感染禽流感病毒的患者的实验数据进行比较，得出了与患者报告一致的患者感染时间的估计值，以及死亡患者的药物疗效估计值低于康复患者的估计值。此外，我们的模型表明，在更严重的流感病毒感染中经常看到的持续的高病毒滴度是抗病毒治疗延迟多达6 dpi仍然会导致病毒滴度降低和疾病缩短的原因。我们的结论是，NAIs可能是一种有效和有益的治疗策略，对更严重的流感病毒株的特点是高，持续，病毒滴度。我们相信，我们的数学模型将是一个有效的工具，指导治疗严重的流感病毒感染的抗病毒药物。(C)2010爱思唯尔有限公司保留所有权利。
Treatment of seasonal influenza viral infections using antivirals such as neuraminidase inhibitors (NAIs) has been proven effective if administered within 48 h post-infection. However, there is growing evidence that antiviral treatment of infections with avian-derived strains even as late as 6 days post-infection (dpi) can significantly reduce infection severity and duration. Using a mathematical model of in-host influenza viral infections which can capture the kinetics of both a short-lived, typical, seasonal infection and a severe infection exhibiting sustained viral titer, we explore differences in the effects of NAI treatment on both types of influenza viral infections. Comparison of our model's behavior against experimental data from patients naturally infected with avian strains yields estimates for the times at which patients were infected that are consistent with those reported by the patients, and estimates of drug efficacies that are lower for patients who died than for those who recovered. In addition, our model suggests that the sustained, high, viral titers often seen in more severe influenza virus infections are the reason why antiviral treatment delayed by as much as 6 dpi will still lead to reduced viral titers and shortened illness. We conclude that NAIs may be an effective and beneficial treatment strategy against more severe strains of influenza virus characterized by high, sustained, viral titers. We believe that our mathematical model will be an effective tool in guiding treatment of severe influenza viral infections with antivirals. (C) 2010 Elsevier Ltd. All rights reserved.